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CD138 multiple myeloma

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https://www.readbyqxmd.com/read/28154173/autocrine-and-paracrine-interactions-between-multiple-myeloma-cells-and-bone-marrow-stromal-cells-by-growth-arrest-specific-gene-6-crosstalk-with-interleukin-6
#1
Miki Furukawa, Hiroshi Ohkawara, Kazuei Ogawa, Kazuhiko Ikeda, Koki Ueda, Akiko Shichishima-Nakamura, Emi Ito, Jun-Ichi Imai, Yuka Yanagisawa, Reiko Honma, Shinya Watanabe, Satoshi Waguri, Takayuki Ikezoe, Yasuchika Takeishi
The pathogenesis of multiple myeloma (MM) has not yet been fully elucidated. Our microarray analysis and immunohistochemistry revealed significant upregulation of growth arrest-specific gene 6 (Gas6), a vitamin K-dependent protein with a structural homology with protein S, in bone marrow (BM) cells of MM patients. ELISA showed that the serum levels of soluble Gas6 were significantly increased in the MM patients when compared with healthy controls. Gas6 was overexpressed in the human CD138-positive MM cell line RPMI-8226...
January 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28148777/sabotaging-of-the-oxidative-stress-response-by-an-oncogenic-noncoding-rna
#2
Nitin Mahajan, Hua-Jun Wu, Richard L Bennett, Catalina Troche, Jonathan D Licht, Jason D Weber, Leonard B Maggi, Michael H Tomasson
Overexpression of the multiple myeloma set domain (MMSET) Wolf-Hirschhorn syndrome candidate 1 gene, which contains an orphan box H/ACA class small nucleolar RNA, ACA11, in an intron, is associated with several cancer types, including multiple myeloma (MM). ACA11 and MMSET are overexpressed cotranscriptionally as a result of the t(4;14) chromosomal translocation in a subset of patients with MM. RNA sequencing of CD138(+) tumor cells from t(4;14)-positive and -negative MM patient bone marrow samples revealed an enhanced oxidative phosphorylation mRNA signature...
February 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28060076/epibulbar-plasmacytoma-masquerading-as-subconjunctival-hemorrhage-in-a-patient-with-multiple-myeloma
#3
Amanda Bradley, Amy Estes, Lane Ulrich, Dilip Thomas, David Gay
PURPOSE: We report a 75-year-old woman with a history of multiple myeloma immunoglobulin D (IgD) variant, who presented with an epibulbar plasmacytoma masquerading as a subconjunctival hemorrhage. METHODS: Magnetic resonance imaging of the brain and orbits with and without contrast was obtained and surgical biopsy of the subconjunctival lesion was performed; histopathology confirmed the diagnosis of plasmacytoma. RESULTS: Subconjunctival biopsy revealed a plasma cell neoplasm infiltrate in the episcleral layer...
February 2017: Cornea
https://www.readbyqxmd.com/read/28056549/pegylated-long-circulating-liposomes-deliver-homoharringtonine-to-suppress-multiple-myeloma-cancer-stem-cells
#4
Miao Li, Fangfang Shi, Xiong Fei, Songyan Wu, Di Wu, Meng Pan, Shouhua Luo, Ning Gu, Jun Dou
The goal of this investigation was to evaluate the inhibiting effect of high proportion polyethyleneglycol of long-circulating homoharringtonine liposomes on RPMI8226 multiple myeloma cancer stem cells. The CD138(-)CD34(-) multiple myeloma cancer stem cells isolated from RPMI8226 cell line using magnetic activated cell sorting system were, respectively, incubated with the optimized formulation of polyethyleneglycol of long-circulating homoharringtonine liposomes and the homoharringtonine in vitro, and the multiple myeloma cancer stem cell proliferation, colony formation, and cell cycle were analyzed...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27995886/-mir-202-contributes-to-sensitizing-mm-cells-to-drug-significantly-via-activing-jnk-sapk-signaling-pathway
#5
Y Zhang, X J Shen, X H Wu, H Cong, H B Ni, S Q Ju, J Y Su
Objective: To explore the role of miR-202 in multiple myeloma (MM) cells, and study the regulation of miR-202 on drug sensitivity of MM cells. Methods: miR-202 and BAFF mRNA levels were detected by real-time PCR. U266 cells were transfected with miR-202-mimics, miR-202-inhibitor, siBAFF and their negative controls. After above treatments, protein levels of Bcl-2 family and MAPK signaling pathway were detected by Western blot analysis, and the proliferation and apoptosis ability of MM cells were examined by WST-1, Annexin V-FLUOS assay, respectively...
November 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/27924158/lycorine-downregulates-hmgb1-to-inhibit-autophagy-and-enhances-bortezomib-activity-in-multiple-myeloma
#6
Mridul Roy, Long Liang, Xiaojuan Xiao, Yuanliang Peng, Yuhao Luo, Weihua Zhou, Ji Zhang, Lugui Qiu, Shuaishuai Zhang, Feng Liu, Mao Ye, Wen Zhou, Jing Liu
Multiple myeloma (MM) is largely incurable and drug-resistant. Novel therapeutic approaches such as inhibiting autophagy or rational drug combinations are aimed to overcome this issue. In this study, we found that lycorine exhibits a promising anti-proliferative activity against MM in vitro and in vivo by inhibiting autophagy. We identified High mobility group box 1 (HMGB1), an important regulator of autophagy, as the most aberrantly expressed protein after lycorine treatment and as a critical mediator of lycorine activity...
2016: Theranostics
https://www.readbyqxmd.com/read/27903712/the-myeloma-stem-cell-concept-revisited-from-phenomenology-to-operational-terms
#7
REVIEW
Hans Erik Johnsen, Martin Bøgsted, Alexander Schmitz, Julie Støve Bødker, Tarec Christoffer El-Galaly, Preben Johansen, Peter Valent, Niklas Zojer, Els Van Valckenborgh, Karin Vanderkerken, Mark van Duin, Pieter Sonneveld, Martin Perez-Andres, Alberto Orfao, Karen Dybkær
The concept of the myeloma stem cell may have important therapeutic implications, yet its demonstration has been hampered by a lack of consistency in terms and definitions. Here, we summarize the current documentation and propose single-cell in vitro studies for future translational studies. By the classical approach, a CD19(-)/CD45(low/-)/CD38(high)/CD138(+) malignant plasma cell, but not the CD19(+)/CD38(low/-) memory B cell compartment, is enriched for tumorigenic cells that initiate myeloma in xenografted immunodeficient mice, supporting that myeloma stem cells are present in the malignant PC compartment...
December 2016: Haematologica
https://www.readbyqxmd.com/read/27903272/inhibition-of-bromodomain-and-extra-terminal-bet-proteins-increases-nkg2d-ligand-mica-expression-and-sensitivity-to-nk-cell-mediated-cytotoxicity-in-multiple-myeloma-cells-role-of-cmyc-irf4-mir-125b-interplay
#8
Maria Pia Abruzzese, Maria Teresa Bilotta, Cinzia Fionda, Alessandra Zingoni, Alessandra Soriani, Elisabetta Vulpis, Cristiana Borrelli, Beatrice Zitti, Maria Teresa Petrucci, Maria Rosaria Ricciardi, Rosa Molfetta, Rossella Paolini, Angela Santoni, Marco Cippitelli
BACKGROUND: Anti-cancer immune responses may contribute to the control of tumors after conventional chemotherapy, and different observations have indicated that chemotherapeutic agents can induce immune responses resulting in cancer cell death and immune-stimulatory side effects. Increasing experimental and clinical evidence highlight the importance of natural killer (NK) cells in immune responses toward multiple myeloma (MM), and combination therapies able to enhance the activity of NK cells against MM are showing promise in treating this hematologic cancer...
December 1, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27902770/mitochondrial-targeted-decyl-triphenylphosphonium-enhances-2-deoxy-d-glucose-mediated-oxidative-stress-and-clonogenic-killing-of-multiple-myeloma-cells
#9
Jeanine Schibler, Ann M Tomanek-Chalkley, Jessica L Reedy, Fenghuang Zhan, Douglas R Spitz, Michael K Schultz, Apollina Goel
Therapeutic advances have markedly prolonged overall survival in multiple myeloma (MM) but the disease currently remains incurable. In a panel of MM cell lines (MM.1S, OPM-2, H929, and U266), using CD138 immunophenotyping, side population staining, and stem cell-related gene expression, we demonstrate the presence of stem-like tumor cells. Hypoxic culture conditions further increased CD138low stem-like cells with upregulated expression of OCT4 and NANOG. Compared to MM cells, these stem-like cells maintained lower steady-state pro-oxidant levels with increased uptake of the fluorescent deoxyglucose analog...
2016: PloS One
https://www.readbyqxmd.com/read/27868410/-expression-of-microrna-221-222-in-patients-with-monoclonal-gammopathy-of-undetermined-significance-and-multiple-myeloma
#10
Suwen Yang, Wei Wang, Hong Jin, Yuhong Zhong, Xinyou Xie
Objective: To detect the expression of miR-221/222 in serum and plasma cells in patients with monoclonal gammopathy of undetermined significance(MGUS) and multiple myeloma(MM), and to explore the possibility of miR-221/222 as biomarkers in the diagnosis and prognosis predicting of MGUS and MM. Methods: Bone marrow and serum samples from 14 patients with newly diagnosed MGUS, 81 patients with newly diagnosed or relapsed MM and 10 controls were collected from Sir Run Run Shaw Hospital of Zhejiang University and Tongde Hospital of Zhejiang Province during January 2013 and December 2015...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/27861307/epibulbar-plasmacytoma-masquerading-as-subconjunctival-hemorrhage-in-a-patient-with-multiple-myeloma
#11
Amanda Bradley, Amy Estes, Lane Ulrich, Dilip Thomas, David Gay
PURPOSE: We report a 75-year-old woman with a history of multiple myeloma immunoglobulin D (IgD) variant, who presented with an epibulbar plasmacytoma masquerading as a subconjunctival hemorrhage. METHODS: Magnetic resonance imaging of the brain and orbits with and without contrast was obtained and surgical biopsy of the subconjunctival lesion was performed; histopathology confirmed the diagnosis of plasmacytoma. RESULTS: Subconjunctival biopsy revealed a plasma cell neoplasm infiltrate in the episcleral layer...
November 16, 2016: Cornea
https://www.readbyqxmd.com/read/27848179/human-mutt-homologue-1-mrna-overexpression-correlates-to-poor-response-of-multiple-myeloma
#12
Huixing Zhou, Yuan Jian, Yun Leng, Nian Liu, Ying Tian, Guorong Wang, Wen Gao, Guangzhong Yang, Wenming Chen
Human MutT homologue 1 (MTH1) is a human 8-oxo-dGTPase that eradicates oxidized bases in the nucleotide pool and DNA. MTH1 is critical for RAS-transformed cancer cell survival, whereas it is dispensable in normal cells and tissues. Here, we determined the expression of MTH1 in multiple myeloma (MM) cell lines and MM patients' CD138 (+) cells and analyzed its potential clinical significance. We detected overexpression of MTH1 mRNA in three cell lines (RPMI 8226, U266, and H929). MTH1 mRNA expression of RPMI8226 was higher than that of U266 and H929...
November 15, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27784369/-correlation-between-expression-of-cd200-and-regulatory-t-cells-in-multiple-myeloma-and-its-significance-in-prognostic-stratification
#13
Ming-Xia Zhu, Wen-Li Wan, Hai-Shen Li, Yan-Fang Wang, Jing Wang, Hui-Sen Ling, Xin-Xing Yan, Xiao-Yan Ke
OBJECTIVE: To study the correlation between expression of CD200 and regulatory T cells (Tregs) in multiple myeloma(MM) patients and to explore its significance in prognostic stratification. METHODS: CD200 and other immunophenotypes, including CD38, CD138, CD56, CD19, CD20, CD117, cytoplasm light chain Kappa and Lambda in bone marrow samples, and Tregs in peripheral blood were detected by flow cytometry from 78 newly diagnosed MM patients. Serum concentrations of hemoglobin(Hb), β2 microglobulin (β2-MG) and lactate dehydrogenase (LDH) were detected, respectively...
October 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27683032/the-role-of-sh3gl3-in-myeloma-cell-migration-invasion-stemness-and-chemo-resistance
#14
Ruoying Chen, Hong Zhao, Dan Wu, Chen Zhao, Weiling Zhao, Xiaobo Zhou
Multiple myeloma (MM) is an incurable cancer characterized by clonal expansion of malignant plasma cells in the bone marrow and their egress into peripheral blood. The mechanisms of myeloma cells migration/invasion have remained unclear. Herein, we found SH3GL3 was highly expressed in the CD138-negative (CD138-) myeloma cells. The migration/invasion capability of CD138- cells was significantly higher than that in the CD138-positive (CD138+) cells. Silencing SH3GL3 using shRNA reduced myeloma cells migration/invasion...
September 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27677741/pharmacogenomics-and-chemical-library-screens-reveal-a-novel-scf-skp2-inhibitor-that-overcomes-bortezomib-resistance-in-multiple-myeloma
#15
E Malek, M A Y Abdel-Malek, S Jagannathan, N Vad, R Karns, A G Jegga, A Broyl, M van Duin, P Sonneveld, F Cottini, K C Anderson, J J Driscoll
While clinical benefit of the proteasome inhibitor (PI) bortezomib for multiple myeloma (MM) patients remains unchallenged, dose-limiting toxicities and drug resistance limit the long-term utility. The E3 ubiquitin (Ub) ligase Skp1-Cullin-1-Skp2 (SCF(Skp2)) promotes proteasomal degradation of the cell cycle inhibitor p27 to enhance tumor growth. Increased SKP2 expression and reduced p27 levels are frequent in human cancers and are associated with therapeutic resistance. SCF(Skp2) activity is increased by the Cullin-1-binding protein Commd1 and the Skp2-binding protein Cks1B...
September 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27634757/cell-adhesion-molecule-cd166-drives-malignant-progression-and-osteolytic-disease-in-multiple-myeloma
#16
Linlin Xu, Khalid S Mohammad, Hao Wu, Colin Crean, Bradley Poteat, Yinghua Cheng, Angelo A Cardoso, Christophe Machal, Helmut Hanenberg, Rafat Abonour, Melissa A Kacena, John Chirgwin, Attaya Suvannasankha, Edward F Srour
Multiple myeloma is incurable once osteolytic lesions have seeded at skeletal sites, but factors mediating this deadly pathogenic advance remain poorly understood. Here, we report evidence of a major role for the cell adhesion molecule CD166, which we discovered to be highly expressed in multiple myeloma cell lines and primary bone marrow cells from patients. CD166(+) multiple myeloma cells homed more efficiently than CD166(-) cells to the bone marrow of engrafted immunodeficient NSG mice. CD166 silencing in multiple myeloma cells enabled longer survival, a smaller tumor burden, and less osteolytic lesions, as compared with mice bearing control cells...
December 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27634301/identification-of-doxorubicin-as-an-inhibitor-of-the-ire1%C3%AE-xbp1-axis-of-the-unfolded-protein-response
#17
Dadi Jiang, Connor Lynch, Bruno C Medeiros, Michaela Liedtke, Rakesh Bam, Arvin B Tam, Zhifen Yang, Muthuraman Alagappan, Parveen Abidi, Quynh-Thu Le, Amato J Giaccia, Nicholas C Denko, Maho Niwa, Albert C Koong
Activation of the IRE1α-XBP1 branch of the unfolded protein response (UPR) has been implicated in multiple types of human cancers, including multiple myeloma (MM). Through an in silico drug discovery approach based on protein-compound virtual docking, we identified the anthracycline antibiotic doxorubicin as an in vitro and in vivo inhibitor of XBP1 activation, a previously unknown activity for this widely utilized cancer chemotherapeutic drug. Through a series of mechanistic and phenotypic studies, we showed that this novel activity of doxorubicin was not due to inhibition of topoisomerase II (Topo II)...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27582537/evaluation-of-in-vitro-effects-of-various-targeted-drugs-on-plasma-cells-and-putative-neoplastic-stem-cells-in-patients-with-multiple-myeloma
#18
Katharina Blatt, Harald Herrmann, Gabriele Stefanzl, Wolfgang R Sperr, Peter Valent
Multiple myeloma (MM) is a malignancy characterized by monoclonal paraproteinemia and tissue plasmocytosis. In advanced MM cytopenia and osteopathy may occur. Although several effective treatment strategies have been developed in recent years, there is still a need to identify new drug targets and to develop more effective therapies for patients with advanced MM. We examined the effects of 15 targeted drugs on growth and survival of primary MM cells and 5 MM cell lines (MM.1S, NCI-H929, OPM-2, RPMI-8226, U-266)...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27557643/treatment-of-acquired-drug-resistance-in-multiple-myeloma-by-combination-therapy-with-xpo1-and-topoisomerase-ii-inhibitors
#19
Joel G Turner, Jana L Dawson, Steven Grant, Kenneth H Shain, William S Dalton, Yun Dai, Mark Meads, Rachid Baz, Michael Kauffman, Sharon Shacham, Daniel M Sullivan
BACKGROUND: Acquired drug resistance is the greatest obstacle to the successful treatment of multiple myeloma (MM). Despite recent advanced treatment options such as liposomal formulations, proteasome inhibitors, immunomodulatory drugs, myeloma-targeted antibodies, and histone deacetylase inhibitors, MM is still considered an incurable disease. METHODS: We investigated whether the clinical exportin 1 (XPO1) inhibitor selinexor (KPT-330), when combined with pegylated liposomal doxorubicin (PLD) or doxorubicin hydrochloride, could overcome acquired drug resistance in multidrug-resistant human MM xenograft tumors, four different multidrug-resistant MM cell lines, or ex vivo MM biopsies from relapsed/refractory patients...
August 24, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27533084/frequency-of-expression-and-generation-of-t-cell-responses-against-antigens-on-multiple-myeloma-cells-in-patients-included-in-the-gmmg-mm5-trial
#20
Michael Schmitt, Angela G Hückelhoven, Michael Hundemer, Anita Schmitt, Susanne Lipp, Martina Emde, Hans Salwender, Mathias Hänel, Katja Weisel, Uta Bertsch, Jan Dürig, Anthony D Ho, Igor Wolfgang Blau, Hartmut Goldschmidt, Anja Seckinger, Dirk Hose
BACKGROUND: Raising T-cell response against antigens either expressed on normal and malignant plasma cells (e.g. HM1.24) or aberrantly on myeloma cells only (e.g. cancer testis antigens, CTA) by vaccination is a potential treatment approach for multiple myeloma. RESULTS: Expression by GEP is found for HM1.24 in all, HMMR in 318/458 (69.4%), MAGE-A3 in 209/458 (45.6%), NY-ESO-1/2 in 40/458 (8.7%), and WT-1 in 4/458 (0.8%) of samples with the pattern being confirmed by RNA-sequencing...
August 11, 2016: Oncotarget
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